Proceedings of the 5th International Conference on Research in Psychology
Year: 2024
DOI:
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Multi-Domain Interactions of TPH2 Predicted by AlphaFold 3
Yasemin Ocak
ABSTRACT:
Serotonin is an important neurotransmitter in learning, memory, happiness, as well as regulating homeostasis. Abnormal levels of serotonin can result in disorders such as depression, OCD, PTSD, schizophrenia, and serotonin syndrome. Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in the production of serotonin. Mutations in TPH2 can result in the disorders discussed above. Thus, TPH2 is a major drug target. TPH2 functions as a homotetramer in the cell, and consists of a catalytic, regulatory, and oligomeric domains. Details of how these domains interact are lacking. Structural insight into TPH2 could help find molecules that regulate its activity. While we do know the structures of the domains separately, we don’t know exactly how they interact. In order to determine how these domains interact, the new technology AlphaFold 3 was used. While AlphaFold 3 is said to have transformed the field of structural biology, in this study we will test whether AlphaFold predictions are accurate by proposing mutants of TPH2 that are at the interface of the regulatory and catalytic domains. Taken together, our efforts will be able to determine if the structure predicted by AlphaFold for a multidomain protein is accurate.
keywords: Serotonin, Tryptophan hydroxylase 2 (TPH2), AlphaFold 3, Depression, OCD, PTSD, Serotonin syndrome, Homotetramer, Catalytic domain, Regulatory domain, Domain interactions, Structural biology, Drug target, Protein structure prediction, TPH2 mutations